Sergeeva Olga, Zhang Yifan, Gao Songqi, Chan E Ricky, Sergeev Maxim, Iyer Renuka, Sexton Sandra, Avril Norbert, Lu Zheng-Rong, Lee Zhenghong
Department of Radiology, Case Western Reserve University, Cleveland, OH, USA.
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA.
J Hepatocell Carcinoma. 2023 Feb 22;10:291-301. doi: 10.2147/JHC.S390939. eCollection 2023.
We tested a recently developed short peptide radioligand for PET imaging of hepatocellular carcinoma (HCC) by targeting an oncoprotein, extra-domain B fibronectin (EDB-FN) in the tumor microenvironment.
The radioligand consists of a small linear peptide ZD2 with Ga-NOTA chelator, and specifically binds to EDB-FN. PET images were acquired dynamically for 1 hour after intravenously (i.v.) injecting 37 MBq (1.0 mCi) of the radioligand into the woodchuck model of naturally occurring HCC. Woodchuck HCC originated from chronic viral hepatitis infection, which recapitulates the corresponding human primary liver cancer. The animals were euthanized post-imaging for tissue collection and validation.
For ZD2 avid liver tumors, the radioligand accumulation plateaued a few minutes after injection, while the liver background uptake stabilized 20 min post-injection. The status of EDB-FN in woodchuck HCC was confirmed by histology and validated by PCR and western blocking.
We have showed the viability of using the ZD2 short peptide radioligand targeting EDB-FN in liver tumor tissue for PET imaging of HCC, which can potentially impact the clinical care for HCC patients.
我们通过靶向肿瘤微环境中的一种癌蛋白——额外结构域B纤连蛋白(EDB-FN),测试了一种最近开发的用于肝细胞癌(HCC)正电子发射断层显像(PET)的短肽放射性配体。
该放射性配体由带有Ga-NOTA螯合剂的小线性肽ZD2组成,可特异性结合EDB-FN。在向自然发生HCC的土拨鼠模型静脉注射37 MBq(1.0 mCi)放射性配体后,动态采集PET图像1小时。土拨鼠HCC起源于慢性病毒感染,可重现相应的人类原发性肝癌。成像后对动物实施安乐死以收集组织并进行验证。
对于ZD2摄取活跃的肝肿瘤,放射性配体在注射后几分钟达到积累平台期,而肝脏本底摄取在注射后20分钟稳定下来。通过组织学确认了土拨鼠HCC中EDB-FN的状态,并通过PCR和蛋白质免疫印迹法进行了验证。
我们已证明使用靶向EDB-FN的ZD2短肽放射性配体对肝肿瘤组织进行HCC的PET成像的可行性,这可能会对HCC患者的临床护理产生影响。